tbuckley/cabot-search huggingface dataset:
Takotsubo syndrome: getting closer to its causes
Authors: Mohammed Majid Akhtar, Victoria L Cammann, Christian Templin, Jelena R Ghadri, Thomas F Lüscher
Journal: Cardiovascular Research (2023)

Abstract Takotsubo syndrome (TTS) accounts for between 1 and 4% of cases presenting clinically as an acute coronary syndrome. It typically presents as a transient cardiac phenotype of left ventricular dysfunction with spontaneous recovery. More dramatic presentations may include cardiogenic shock or cardiac arrest. Despite progress in the understanding of the condition since its first description in 1990, considerable questions remain into understanding underlying pathomechanisms. In this review article, we describe the current published data on potential underlying mechanisms associated with the onset of TTS including sympathetic nervous system over-stimulation, structural and functional alterations in the central nervous system, catecholamine secretion, alterations in the balance and distribution of adrenergic receptors, the additive impact of hormones including oestrogen, epicardial coronary or microvascular spasm, endothelial dysfunction, and genetics as potentially contributing to the cascade of events leading to the onset. These pathomechanisms provide suggestions for novel potential therapeutic strategies in patients with TTS including the role of cognitive behavioural therapy, beta-blockers, and endothelin-A antagonists. The underlying mechanism of TTS remains elusive. In reality, physical or emotional stressors likely trigger through the amygdala and hippocampus a central neurohumoral activation with the local and systemic secretion of excess catecholamine and other neurohormones, which exert its effect on the myocardium through a metabolic switch, altered cellular signalling, and endothelial dysfunction. These complex pathways exert a regional activation in the myocardium through the altered distribution of adrenoceptors and density of autonomic innervation as a protective mechanism from myocardial apoptosis. More research is needed to understand how these different complex mechanisms interact with each other to bring on the TTS phenotype.
A New Chromosome-Assigned Mongolian Gerbil Genome Allows Characterization of Complete Centromeres and a Fully Heterochromatic Chromosome
Authors: Thomas D Brekke, Alexander S T Papadopulos, Eva Julià, Oscar Fornas, Beiyuan Fu, Fengtang Yang, Roberto de la Fuente, Jesus Page, Tobias Baril, Alexander Hayward, John F Mulley
Journal: Molecular Biology and Evolution (2023)

Abstract Chromosome-scale genome assemblies based on ultralong-read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus), which includes the complete sequence of all centromeres. Gerbils are thus the one of the first vertebrates to have their centromeres completely sequenced. Gerbil centromeres are composed of four different repeats of length 6, 37, 127, or 1,747 bp, which occur in simple alternating arrays and span 1–6 Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intraarm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (&amp;gt;150 kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data and highlight novel patterns involved in the evolution of chromosomes.
Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial
Authors: Mikail Gögenur, Lukas Balsevicius, Mustafa Bulut, Nesibe Colak, Tobias Freyberg Justesen, Anne-Marie Kanstrup Fiehn, Marianne Bøgevang Jensen, Kathrine Høst-Rasmussen, Britt Cappelen, Shruti Gaggar, Asma Tajik, Jawad Ahmad Zahid, Astrid Louise Bjørn Bennedsen, Tommaso Del Buono D’Ondes, Hans Raskov, Susanne Gjørup Sækmose, Lasse Bremholm Hansen, Ali Salanti, Susanne Brix, Ismail Gögenur
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm 2 , p&lt;0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value&lt;0.05) and downregulation of FOXP3 (adjusted p value&lt;0.05). Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts. Trial registration number NCT04591379 .
The VGNC: expanding standardized vertebrate gene nomenclature
Authors: Tamsin E M Jones, Bethan Yates, Bryony Braschi, Kristian Gray, Susan Tweedie, Ruth L Seal, Elspeth A Bruford
Journal: Genome biology (2023)

The Vertebrate Gene Nomenclature Committee (VGNC) was established in 2016 as a sister project to the HUGO Gene Nomenclature Committee, to approve gene nomenclature in vertebrate species without an existing dedicated nomenclature committee. The VGNC aims to harmonize gene nomenclature across selected vertebrate species in line with human gene nomenclature, with orthologs assigned the same nomenclature where possible. This article presents an overview of the VGNC project and discussion of key findings resulting from this work to date. VGNC-approved nomenclature is accessible at https://vertebrate.genenames.org and is additionally displayed by the NCBI, Ensembl, and UniProt databases.
Tumor-Associated Retinal Pigmentation in Choroidal Melanoma
Authors: Alexander Wallace, Yamini Krishna, Sarah E. Coupland, Heinrich Heimann, Asterios Diafas, Rumana N. Hussain
Journal: Ophthalmology (2023)

To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology.Imaging and histologic analysis of a retrospective cohort of patients.Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023.Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA).Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated.Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51-88 years). The median largest basal diameter was 16.10 mm (range, 9.17-21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40-13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68+ melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative.Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies.The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Succinate based polymers drive immunometabolism in dendritic cells to generate cancer immunotherapy
Authors: Sahil Inamdar, Abhirami P. Suresh, Joslyn L. Mangal, Nathan D. Ng, Alison Sundem, Hoda Shokrollahzadeh Behbahani, Thomas E. Rubino, Xiaojian Shi, Sharon T. Loa, Jordan R. Yaron, Taro Hitosugi, Matthew Green, Haiwei Gu, Marion Curtis, Abhinav P. Acharya
Journal: Journal of Controlled Release (2023)
Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer
Authors: Vanessa Ortiz-Barahona, Marta Soler, Veronica Davalos, Carlos A. García-Prieto, Maxime Janin, Fernando Setien, Irene Fernández-Rebollo, Joan J. Bech-Serra, Carolina De La Torre, Sonia Guil, Alberto Villanueva, Pei-Hong Zhang, Li Yang, Marco Guarnacci, Ulrike Schumann, Thomas Preiss, Ugne Balaseviciute, Robert Montal, Josep M. Llovet, Manel Esteller
Journal: Molecular Cancer (2023)

RNA modifications are important regulators of transcript activity and an increasingly emerging body of data suggests that the epitranscriptome and its associated enzymes are altered in human tumors.
The influence of transposable elements on animal colouration
Authors: James D. Galbraith, Alexander Hayward
Journal: Trends in Genetics (2023)

Transposable elements (TEs) are mobile genetic sequences present within host genomes. TEs can contribute to the evolution of host traits, since transposition is mutagenic and TEs often contain host regulatory and protein coding sequences. We review cases where TEs influence animal colouration, reporting major patterns and outstanding questions. TE-induced colouration phenotypes typically arise via introduction of novel regulatory sequences and splice sites, affecting pigment cell development or pigment synthesis. We discuss if particular TE types may be more frequently involved in the evolution of colour variation in animals, given that examples involving long terminal repeat (LTR) elements appear to dominate. Currently, examples of TE-induced colouration phenotypes in animals mainly concern model and domesticated insect and mammal species. However, several influential recent examples, coupled with increases in genome sequencing, suggest cases reported from wild species will increase considerably.
Advanced bioactive glue tethering Lubricin/PRG4 to promote integrated healing of avascular meniscus tears
Authors: Solaiman Tarafder, Jaskirti Ghataure, David Langford, Rachel Brooke, Ryunhyung Kim, Samantha Lewis Eyen, Julian Bensadoun, Jeffrey T. Felix, James L. Cook, Chang H. Lee
Journal: Bioactive Materials (2023)

Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone, but no regenerative therapy exist. Previously, we showed that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) via fibrin-based bio-glue facilitate meniscus healing by inducing recruitment and stepwise differentiation of synovial mesenchymal stem/progenitor cells. Here, we first explored the potential of genipin, a natural crosslinker, to enhance fibrin-based glue's mechanical and degradation properties. In parallel, we identified the harmful effects of lubricin on meniscus healing and investigated the mechanism of lubricin deposition on the injured meniscus surface. We found that the pre-deposition of hyaluronic acid (HA) on the torn meniscus surface mediates lubricin deposition. Then we implemented chemical modifications with heparin conjugation and CD44 on our bioactive glue to achieve strong initial bonding and integration of lubricin pre-coated meniscal tissues. Our data suggested that heparin conjugation significantly enhances lubricin-coated meniscal tissues. Similarly, CD44, exhibiting a strong binding affinity to lubricin and hyaluronic acid (HA), further improved the integrated healing of HA/lubricin pre-coated meniscus injuries. These findings may represent an important foundation for developing a translational bio-active glue guiding the regenerative healing of meniscus injuries.
Long-Term Clinical Outcome of Major Adverse Cardiac Events in Survivors of Infective Endocarditis
Authors: Chia-Jen Shih, Hsi Chu, Pei-Wen Chao, Yi-Jung Lee, Shu-Chen Kuo, Szu-Yuan Li, Der-Cherng Tarng, Chih-Yu Yang, Wu-Chang Yang, Shuo-Ming Ou, Yung-Tai Chen
Journal: Circulation (2014)

Background— Substantial infective endocarditis (IE)–related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. Methods and Results— A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40–1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90–2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17–1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05–2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44–1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14–2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. Conclusion— Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.
A Gd-doped Mg-Al-LDH/Au nanocomposite for CT/MR bimodal imagings and simultaneous drug delivery
Authors: Lijun Wang, Huaiyong Xing, Shengjian Zhang, Qingguo Ren, Limin Pan, Kun Zhang, Wenbo Bu, Xiangpeng Zheng, Liangping Zhou, Weijun Peng, Yanqing Hua, Jianlin Shi
Journal: Biomaterials (2013)
Reply to Tianrui Feng, Miao Ren, and Zhien Zhou’s Letter to the Editor re: Peter Fletcher, Marta De Santis, Simona Ippoliti, et al. Vector Prostate Biopsy: A Novel Magnetic Resonance Imaging/Ultrasound Image Fusion Transperineal Biopsy Technique Using Electromagnetic Needle Tracking Under Local Anaesthesia. Eur Urol 2023;83:249–56
Authors: Peter Fletcher, Christof Kastner
Journal: European Urology (2023)
2022 Update on Prostate Cancer Epidemiology and Risk Factors—A Systematic Review
Authors: Oskar Bergengren, Kelly R. Pekala, Konstantina Matsoukas, Jonathan Fainberg, Sean F. Mungovan, Ola Bratt, Freddie Bray, Otis Brawley, Amy N. Luckenbaugh, Lorelei Mucci, Todd M. Morgan, Sigrid V. Carlsson
Journal: European Urology (2023)
Reply to: The Race Arithmetic of the Global Lung Function Initiative Global Reference Equations
Authors: Cole Bowerman, Nirav R. Bhakta, Danny Brazzale, Brendan G. Cooper, Julie Cooper, Laura Gochicoa-Rangel, Jeffrey Haynes, David A. Kaminsky, Le Thi Tuyet Lan, Refiloe Masekela, Meredith C. McCormack, Irene Steenbruggen, Sanja Stanojevic
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: The Race Arithmetic of the GLI Global Reference Equations." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Beyond antioxidation: Harnessing the CeO2 nanoparticles as a renoprotective contrast agent for in vivo spectral CT angiography
Authors: Cai Feng, Zongling Xiong, Xianting Sun, Hao Zhou, Tianming Wang, Ying Wang, Harrison X. Bai, Peng Lei, Weihua Liao
Journal: Biomaterials (2023)
Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial
Authors: Miriam Santer, Megan Lawrence, Susanne Renz, Zina Eminton, Beth Stuart, Tracey H Sach, Sarah Pyne, Matthew J Ridd, Nick Francis, Irene Soulsby, Karen Thomas, Natalia Permyakova, Paul Little, Ingrid Muller, Jacqui Nuttall, Gareth Griffiths, Kim S Thomas, Alison M Layton
Journal: BMJ (2023)

Abstract Objective To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. Design Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. Setting Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. Participants Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. Interventions Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. Main outcome measures Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator’s global assessment (IGA) for treatment success; and adverse reactions. Results From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. Conclusions Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. Trial registration ISRCTN12892056
Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma
Authors: Michael L. Wang, Wojciech Jurczak, Pier Luigi Zinzani, Toby A. Eyre, Chan Y. Cheah, Chaitra S. Ujjani, Youngil Koh, Koji Izutsu, James N. Gerson, Ian Flinn, Benoit Tessoulin, Alvaro J. Alencar, Shuo Ma, David Lewis, Ewa Lech-Maranda, Joanna Rhodes, Krish Patel, Kami Maddocks, Nicole Lamanna, Yucai Wang, Constantine S. Tam, Talha Munir, Hirokazu Nagai, Francisco Hernandez-Ilizaliturri, Anita Kumar, Timothy S. Fenske, John F. Seymour, Andrew D. Zelenetz, Binoj Nair, Donald E. Tsai, Minna Balbas, Richard A. Walgren, Paolo Abada, Chunxiao Wang, Junjie Zhao, Anthony R. Mato, Nirav N. Shah
Journal: Journal of Clinical Oncology (2023)

Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis.Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety.The median patient age was 70 years (range, 46-87), the median prior lines of therapy was 3 (range, 1-8), 82.2% had discontinued a prior cBTKi because of disease progression, and 77.8% had intermediate- or high-risk simplified MCL International Prognostic Index score. The ORR was 57.8% (95% CI, 46.9 to 68.1), including 20.0% complete responses (n = 18). At a median follow-up of 12 months, the median DOR was 21.6 months (95% CI, 7.5 to not reached). The 6- and 12-month estimated DOR rates were 73.6% and 57.1%, respectively. In the MCL safety cohort (n = 164), the most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). Grade ≥3 TEAEs of hemorrhage (3.7%) and atrial fibrillation/flutter (1.2%) were less common. Only 3% of patients discontinued pirtobrutinib because of a treatment-related adverse event.Pirtobrutinib is a first-in-class novel noncovalent (reversible) BTKi and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated R/R MCL. Pirtobrutinib was well tolerated with low rates of treatment discontinuation because of toxicity.